Immunohistochemical analysis of NOTCH1 and JAGGED1 expression in multiple myeloma and monoclonal gammopathy of undetermined significance
Immunohistochemical analysis of NOTCH1 and JAGGED1 expression in multiple myeloma and monoclonal gammopathy of undetermined significance
复制标题
DOI：
10.1016/j.humpath.2010.05.002
复制
发表时间：
2010-12-01
期刊：
影响因子：
3.3
通讯作者：
Dominis, Mara
中科院分区：
文献类型：
--
作者：
Skrtic, Anita;Korac, Petra;Dominis, Mara
Notch信号转导与多发性骨髓瘤的发病机制有关，多发性骨髓瘤在肿瘤浆细胞中表达高水平的活性Notch蛋白NOTCH 1和JAGGED 1。应用免疫组化方法对80例初诊多发性骨髓瘤和20例临床意义不明的单克隆丙种球蛋白病患者骨髓环钻活检标本进行检测，计数每1000个肿瘤细胞中的阳性肿瘤细胞数，并半定量评估染色强度。77例（59.7%）病例中绝大多数病例NOTCH 1染色强，而JAGGED 1染色弱（676%的病例）相比之下，在所有意义不明的单克隆丙种球蛋白病病例中，这两种标志物均呈阴性。然而，当疾病从意义不明的单克隆丙种球蛋白病进展为多发性骨髓瘤时，（见于4名患者），随后的骨髓活检分析显示肿瘤浆细胞中两种标记物的弱表达。将免疫组织化学结果与骨髓浸润、浆细胞分化和t（11，14）（q13，q32）t（14，16）（q32，q23）和t（4，14）（第16页第3页，q23）和多发性骨髓瘤患者的总生存率多发性骨髓瘤浆细胞中的NOTCH 1强染色与骨髓浸润的弥漫型（P= 0.02）和浆细胞的不成熟形态类型（P = 0.43）之间存在显著相关性。截至203个月，在多发性骨髓瘤患者中，NOTCH 1（P = 484）和JAGGED 1（P = 822）阳性和阴性病例的总生存期无差异。我们的研究结果表明，NOTCH1和JAGGED 1表达在浆细胞瘤形成中的重要性，以及它们对多发性骨髓瘤骨髓抑制的免疫组化评价的可能诊断价值（C）2010爱思唯尔公司版权所有
Notch signaling is implicated in the pathogenesis of multiple myeloma expressing high level of active Notch proteins NOTCH1 and JAGGED1 in tumor plasma cells We investigated expression of NOTCH! and JAGGED1 in bone marrow trephine biopsies of 80 newly diagnosed multiple myeloma and 20 monoclonal gammopathy of undetermined significance patients using immunohistochemical methods The number of positive tumor cells was counted per 1000 tumor cells and the intensity of staining was assessed semi quantitatively Multiple myelomas expressed NOTCH1 in 92 31% (72/78) and JAGGED1 in 92 21% (71/77) cases NOTCH1 staining was strong in the majority of cases (59 7%), whereas JAGGED1 was predominately weak (67 6% of cases) In contrast, both markers were negative in all monoclonal gammopathy of undetermined significance cases However, upon progression of disease from monoclonal gammopathy of undetermined significance to multiple myeloma (seen in 4 patients), analysis of the subsequent bone marrow biopsy showed weak expression of both markers in tumorous plasma cells Immunohistochemistry results were compared with the pattern of bone marrow infiltration, plasma cell differentiation, and the presence of t(11,14)(q13,q32) t(14,16)(q32,q23),and t(4,14)(p16 3,q23) and overall survival in multiple myeloma patients A significant correlation was found between strong NOTCH1 staining in multiple myeloma plasma cells and the diffuse type of bone marrow infiltration (P= 002) and an immature morphologic type of plasma cells (P = 043) After a median follow-up of 203 months, in multiple myeloma patients no difference in overall survival between NOTCH1 (P = 484) and JAGGED1 (P = 822) positive and negative cases were found In conclusion, our results indicate importance of NOTCH1 and JAGGED1 expression in plasma cell neoplasia and a possible diagnostic value of their immunohistochemical evaluation of bone marrow Infiltrates for multiple myeloma (C) 2010 Elsevier Inc All rights reserved